-
British Journal of Sports Medicine Aug 2023To estimate the efficacy of exercise on depressive symptoms compared with non-active control groups and to determine the moderating effects of exercise on depression and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the efficacy of exercise on depressive symptoms compared with non-active control groups and to determine the moderating effects of exercise on depression and the presence of publication bias.
DESIGN
Systematic review and meta-analysis with meta-regression.
DATA SOURCES
The Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, Embase, SPORTDiscus, PsycINFO, Scopus and Web of Science were searched without language restrictions from inception to 13 September2022 (PROSPERO registration no CRD42020210651).
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials including participants aged 18 years or older with a diagnosis of major depressive disorder or those with depressive symptoms determined by validated screening measures scoring above the threshold value, investigating the effects of an exercise intervention (aerobic and/or resistance exercise) compared with a non-exercising control group.
RESULTS
Forty-one studies, comprising 2264 participants post intervention were included in the meta-analysis demonstrating large effects (standardised mean difference (SMD)=-0.946, 95% CI -1.18 to -0.71) favouring exercise interventions which corresponds to the number needed to treat (NNT)=2 (95% CI 1.68 to 2.59). Large effects were found in studies with individuals with major depressive disorder (SMD=-0.998, 95% CI -1.39 to -0.61, k=20), supervised exercise interventions (SMD=-1.026, 95% CI -1.28 to -0.77, k=40) and moderate effects when analyses were restricted to low risk of bias studies (SMD=-0.666, 95% CI -0.99 to -0.34, k=12, NNT=2.8 (95% CI 1.94 to 5.22)).
CONCLUSION
Exercise is efficacious in treating depression and depressive symptoms and should be offered as an evidence-based treatment option focusing on supervised and group exercise with moderate intensity and aerobic exercise regimes. The small sample sizes of many trials and high heterogeneity in methods should be considered when interpreting the results.
Topics: Humans; Depression; Depressive Disorder, Major; Exercise; Exercise Therapy
PubMed: 36731907
DOI: 10.1136/bjsports-2022-106282 -
BMJ (Clinical Research Ed.) Feb 2024To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions.
DESIGN
Systematic review and network meta-analysis.
METHODS
Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Bayesian arm based, multilevel network meta-analyses were performed for the primary analyses. Quality of the evidence for each arm was graded using the confidence in network meta-analysis (CINeMA) online tool.
DATA SOURCES
Cochrane Library, Medline, Embase, SPORTDiscus, and PsycINFO databases.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Any randomised trial with exercise arms for participants meeting clinical cut-offs for major depression.
RESULTS
218 unique studies with a total of 495 arms and 14 170 participants were included. Compared with active controls (eg, usual care, placebo tablet), moderate reductions in depression were found for walking or jogging (n=1210, κ=51, Hedges' g -0.62, 95% credible interval -0.80 to -0.45), yoga (n=1047, κ=33, g -0.55, -0.73 to -0.36), strength training (n=643, κ=22, g -0.49, -0.69 to -0.29), mixed aerobic exercises (n=1286, κ=51, g -0.43, -0.61 to -0.24), and tai chi or qigong (n=343, κ=12, g -0.42, -0.65 to -0.21). The effects of exercise were proportional to the intensity prescribed. Strength training and yoga appeared to be the most acceptable modalities. Results appeared robust to publication bias, but only one study met the Cochrane criteria for low risk of bias. As a result, confidence in accordance with CINeMA was low for walking or jogging and very low for other treatments.
CONCLUSIONS
Exercise is an effective treatment for depression, with walking or jogging, yoga, and strength training more effective than other exercises, particularly when intense. Yoga and strength training were well tolerated compared with other treatments. Exercise appeared equally effective for people with and without comorbidities and with different baseline levels of depression. To mitigate expectancy effects, future studies could aim to blind participants and staff. These forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments for depression.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42018118040.
Topics: Humans; Network Meta-Analysis; Depression; Depressive Disorder, Major; Bayes Theorem; Exercise; Antidepressive Agents; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38355154
DOI: 10.1136/bmj-2023-075847 -
Psychiatry Research Nov 2023The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive... (Meta-Analysis)
Meta-Analysis Review
The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in depression severity, determined by calculating the change in depression ratings from baseline to the primary endpoint in the psilocybin arm versus the control arm. The literature search yielded 1734 studies, and 13 studies (n = 686) were included in either qualitative and/or quantitative analyses. The meta-analysis included 9 studies (pooled n = 596) and yielded a large effect size in favour of psilocybin (SMD = -0.78; p<0.001). Risk ratios for response and remission were large and significant in favour of psilocybin. A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence for antidepressant efficacy with psilocybin-assisted psychotherapy, however, further studies are needed to evaluate safety and efficacy and to optimize treatment protocols.
Topics: Humans; Psilocybin; Depression; Depressive Disorder, Major; Psychotherapy; Antidepressive Agents; Hallucinogens
PubMed: 37844352
DOI: 10.1016/j.psychres.2023.115531 -
The Lancet. Psychiatry Sep 2023Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines required updated evidence synthesis to improve their current recommendations. In order to inform evidence-based prescribing, we investigated the comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression.
METHODS
We conducted a systematic review and network meta-analysis. We searched for randomised controlled trials comparing pharmacological interventions with each other or placebo in adults with acute bipolar depression (type I, type II, or not otherwise specified), excluding those with substance misuse, unipolar depression, or schizophrenia, in MEDLINE, Embase, PsycINFO, Google Scholar, Cochrane Library, Web of Knowledge, CINAHL, and LILACS from database inception up to April 13, 2023. Criteria for eligibility were a duration of 2-16 weeks with masked outcome assessments, and we included combination, add-on design, and monotherapy studies. The co-primary outcomes were depressive symptoms, examined with standardised mean differences (SMDs), and manic switch, examined with odds ratios (ORs). We also investigated dropouts due to any reason, inefficacy, adverse events, and important side-effects as secondary outcomes. The confidence in the evidence was evaluated using Confidence-In-Network-Meta-Analysis (CINeMA). The study was registered with PROSPERO, CRD42020171726.
RESULTS
We analysed data from 101 randomised controlled trials covering 20 081 participants, 8063 men (41·7%) and 11 263 women (58·3%; sex not available in four studies), mean age 41·0 years (range of means 28·7-53·6 years), and 68 medications and placebo. Ethnicity data were not available. With moderate confidence in the evidence, olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were more efficacious than placebo in reducing depressive symptoms, with SMDs ranging from 0·41 (95% CI 0·19-0·64) for olanzapine plus fluoxetine to 0·16 (0·03-0·29) for lamotrigine. Several other drugs might also be efficacious, but the confidence in the evidence was very low to low. Antidepressants as a class seem to be efficacious, but had a higher risk for manic switch compared to antipsychotics. Medications differed in their side-effect profiles.
INTERPRETATION
This is, to our knowledge, the largest network meta-analysis of pharmacotherapy for bipolar depression to date. Olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were found to be more efficacious than placebo in adults with acute bipolar depression, with good confidence in the evidence, and to differ in their side-effect profiles. These findings can inform evidence-based care and the development of treatment guidelines internationally.
FUNDING
None.
Topics: Male; Adult; Female; Humans; Middle Aged; Bipolar Disorder; Depression; Fluoxetine; Lamotrigine; Olanzapine; Lurasidone Hydrochloride; Quetiapine Fumarate; Network Meta-Analysis; Drug-Related Side Effects and Adverse Reactions
PubMed: 37595997
DOI: 10.1016/S2215-0366(23)00199-2 -
The World Journal of Biological... 2023Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the... (Review)
Review
Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the accessibility and scalability of oral ketamine make it preferred over intravenous ketamine. In this systematic review, we aim to evaluate the efficacy, tolerability, and safety of oral ketamine, esketamine and r-ketamine for unipolar and bipolar depression. Electronic databases were searched from inception to September 2022 to identify relevant articles. Twenty-two studies, including four randomized clinical trials (RCTs), one case series, six case reports, five open-label trials and six retrospective chart review studies involving 2336 patients with depression were included. All included studies reported significant improvement following ketamine administration. Ketamine was well tolerated without serious adverse events. However, RCTs had a high risk of bias due to analysis methods and adverse events monitoring. Ketamine dosage varied from 0.5 to 1.25 mg/kg. The frequency of administration was daily to monthly. Several important limitations were identified, most notably the small number of RCTs. Taken together, preliminary evidence suggests the potential for antidepressant effect of oral ketamine. However, further research with large sample size and long follow-up period is needed to better determine the antisuicidal effect and efficacy in treatment-resistant depression.
Topics: Humans; Ketamine; Depression; Excitatory Amino Acid Antagonists; Bipolar Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
PubMed: 36651238
DOI: 10.1080/15622975.2023.2169349 -
Psychiatry Research Sep 2023Major depressive disorder [MDD] is expected to be the leading cause of overall global burden of disease by the year 2030 [WHO]. Non-response to first line... (Review)
Review
BACKGROUND
Major depressive disorder [MDD] is expected to be the leading cause of overall global burden of disease by the year 2030 [WHO]. Non-response to first line pharmacological and psychotherapeutic antidepressive treatments is substantial, with treatment-resistant depression [TRD] affecting approximately one third of depressed patients. There is an urgent need for rapid acting and effective treatments in this population. Repetitive Transcranial Magnetic Stimulation [rTMS] is an non-invasive treatment option for patients with MDD or TRD. Recent studies have proposed new paradigms of TMS, one paradigm is accelerated intermittent Theta Burst Stimulation [aiTBS].
OBJECTIVE
This systematic review assesses the efficacy, safety and tolerability of aiTBS in patients with MDD.
METHODS
This review was registered with PROSPERO [ID number: 366556]. A systematic literature review was performed using Pubmed, Web of Science and PsycINFO. Case reports/series, open-label and randomized controlled trials [RCTs] were eligible for inclusion if they met the following criteria; full text publication available in English describing a form of aiTBS for MDD or TRD. aiTBS was defined as at least three iTBS treatments sessions per day, during at least four days for one week.
RESULTS
32 studies were identified describing aiTBS in MDD, 13 studies described overlapping samples. Six articles from five unique studies met eligibility criteria; two open-label studies and three RCTs [two double blind and one quadruple blind]. Response rates directly after treatment ranged from 20.0% to 86.4% and remission rates ranged from 10.0 to 86.4%. Four weeks after treatment response rates ranged from 0.0% to 66.7% and remission rates ranged from 0.0% to 57.1%. Three articles described a significant reduction in suicidality scores. aiTBS was well tolerated and safe, with no serious adverse events reported.
CONCLUSIONS
aiTBS is a promising form of non-invasive brain stimulation [NIBS] with rapid antidepressant and antisuicidal effects in MDD. Additionally, aiTBS was well tolerated and safe. However, the included studies had small samples sizes and differed in frequency, intersession interval, neuro localization and stimulation intensity. Replication studies and larger RCTs are warranted to establish efficacy, safety and long term effects.
Topics: Humans; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Depressive Disorder, Treatment-Resistant; Stereotaxic Techniques; Randomized Controlled Trials as Topic
PubMed: 37625365
DOI: 10.1016/j.psychres.2023.115429 -
Neuroscience and Biobehavioral Reviews Sep 2023This review and meta-analysis aimed to describe the existing literature on interventions for bipolar disorder (BD) targeting the 6 pillars of Lifestyle Psychiatry: diet,... (Meta-Analysis)
Meta-Analysis Review
This review and meta-analysis aimed to describe the existing literature on interventions for bipolar disorder (BD) targeting the 6 pillars of Lifestyle Psychiatry: diet, physical activity (PA), substance use (SU), sleep, stress management, and social relationships (SR). Randomized Controlled Trials that examined the efficacy of lifestyle interventions targeting improvement in depressive/(hypo)manic symptom severity, lifestyle patterns, functioning, quality of life, and/or circadian rhythms were included. The systematic review included 18 studies, while the meta-analysis included studies targeting the same lifestyle domains and outcomes. Sleep (n = 10), PA (n = 9), and diet (n = 8) were the most targeted domains, while SU, SM and SR were least targeted (n = 4 each). Combined diet and PA interventions led to significant improvements in depressive symptoms (SMD: -0.46; 95%CI: -0.88, -0.04; p = 0.03), and functioning (SMD: -0.47; 95%CI: -0.89, -0.05; p = 0.03). Sleep interventions also led to significant improvements in depressive symptoms (SMD: -0.80; 95%CI: -1.21, -0.39; p < 0.01). Future research should focus on developing more multidimensional lifestyle interventions for a potentially greater impact on clinical and functional outcomes of BD.
Topics: Humans; Bipolar Disorder; Quality of Life; Life Style; Exercise; Psychotherapy
PubMed: 37263531
DOI: 10.1016/j.neubiorev.2023.105257 -
The Lancet. Psychiatry Nov 2023Side-effects of psychiatric medication impair quality of life and functioning. Furthermore, they contribute to morbidity, mortality, stigma, and poor treatment...
BACKGROUND
Side-effects of psychiatric medication impair quality of life and functioning. Furthermore, they contribute to morbidity, mortality, stigma, and poor treatment concordance resulting in relapse of psychiatric illness. Guidelines recommend discussing side-effects with patients when making treatment decisions, but a synthesis of antidepressant and antipsychotic side-effects to guide this process is missing, and considering all side-effects is a complex, multidimensional process. We aimed to create comprehensive databases of antipsychotic and antidepressant side-effects, and a digital tool to support database navigation.
METHODS
To create the databases, we did an umbrella review of Embase, PsycINFO, and MEDLINE from database inception to June 26, 2023. We included meta-analyses of randomised controlled trials examining antipsychotic monotherapy in the treatment of schizophrenia or antidepressant monotherapy in the treatment of major depressive disorder. We included meta-analyses in adults (aged ≥18 years) that assessed drugs with a common comparator. The search was complemented by a review of national and international guidelines and consensus statements for the treatment of major depressive disorder and schizophrenia in adults. Effect sizes for antipsychotic and antidepressant side-effects were extracted from meta-analyses examining the largest number of drugs. In cases of incomplete meta-analytic coverage, data were imputed on the basis of guideline-derived ordinal rankings or, if imputation was not possible, ordinal scores were extracted. Both meta-analytic and ordinal outcomes were normalised to provide values between 0 and 1. We then constructed a digital tool, the Psymatik Treatment Optimizer, to combine the side-effect databases with side-effect concerns of an individual user, to enable users to select side-effects of concern and the relative degree of concern for each side-effect. Concern weightings and the side-effect databases are synthesised via a multicriteria decision analysis method (technique for order of preference by similarity to ideal situation, or TOPSIS).
FINDINGS
Of 3724 citations, 14 articles containing 68 meta-analyses of individual side-effects met inclusion criteria. After review of 19 guidelines, seven provided ordinal data. Antipsychotic data were extracted from five studies (11 meta-analyses, n=65 594 patients) and four guidelines, and antidepressant data were extracted from three guidelines. The resultant databases included data on 32 antipsychotics (14 side-effects) and 37 antidepressants (nine side-effects). The databases highlighted the clinical dilemma associated with balancing side-effects, with avoidance of one side-effect (eg, weight gain for antipsychotics) increasing the risk of others (eg, akathisia). To aid with this dilemma, the Psymatik Treatment Optimizer synthesises the side-effect databases with individual user-defined concern weights. After computing up to 5851 pairwise comparisons for antidepressants and 5142 pairwise comparisons for antipsychotics, Psymatik ranks treatments in order of preference for the individual user, with the output presented in a heatmap.
INTERPRETATION
By facilitating collaborative, personalised, and evidence-based prescribing decisions, the side-effect databases and digital application supports care delivery that is consistent with international regulatory guidance for the treatment of schizophrenia and depression, and it therefore has promise for informing psychiatric practice and improving outcomes.
FUNDING
National Institute for Health and Care Research, Maudsley Charity, Wellcome Trust, Medical Research Council.
Topics: Adult; Humans; Adolescent; Antipsychotic Agents; Depressive Disorder, Major; Quality of Life; Antidepressive Agents; Schizophrenia
PubMed: 37774723
DOI: 10.1016/S2215-0366(23)00262-6 -
Journal of Affective Disorders Oct 2023The concurrent assessment of weight and affective psychopathology outcomes relevant to the psychopharmacology of major eating disorders (EDs), namely anorexia nervosa... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The concurrent assessment of weight and affective psychopathology outcomes relevant to the psychopharmacology of major eating disorders (EDs), namely anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), warrants systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
PubMed, Scopus, and ClinicalTrials.gov were inquired from inception through August 31st, 2022, for RCTs documenting any psychopharmacological intervention for EDs diagnosed according to validated criteria and reporting weight and psychopathology changes. Adopted keywords were: "anorexia nervosa," "bulimia nervosa," "binge eating disorder," "antidepressant," "antipsychotic," and "mood stabilizer." No language restriction applied.
RESULTS
5122 records were identified, and 203 full-texts were reviewed. Sixty-two studies entered the qualitative synthesis (AN = 22, BN = 23, BED = 17), of which 22 entered the meta-analysis (AN = 9, BN = 10, BED = 3). Concerning BMI increase in AN, olanzapine outperformed placebo (Hedges'g = 0.283, 95%C·I. = 0.051-0.515, I = 0 %; p = .017), whereas fluoxetine failed (Hedges'g = 0.351, 95%C.I. = -0.248 to 0.95, I = 63.37 %; p = .251). Fluoxetine not significantly changed weight (Hedges'g = 0.147, 95%C.I. = -0.157-0.451, I = 0 %; p = .343), reducing binging (Hedges'g = 0.203, 95%C.I. = 0.007-0.399, I = 0 %; p = .042), and purging episodes (Hedges'g = 0.328, 95%C.I. = -0.061-0.717, I = 58.97 %; p = .099) in BN. Lisdexamfetamine reduced weight (Hedges'g = 0.259, 95%C.I. = 0.071-0.446, I = 0 %; p = .007) and binging (Hedges'g = 0.571, 95%C.I. = 0.282-0.860, I = 53.84 %; p < .001) in BED.
LIMITATIONS
Small sample size, short duration, and lack of reliable operational definitions affect most of the included sponsored RCTs.
CONCLUSIONS
The efficacy of different drugs varies across different EDs, warranting additional primary studies recording broad psychopathological and cardiometabolic outcomes besides weight, especially against established psychotherapy interventions.
Topics: Humans; Fluoxetine; Psychopharmacology; Randomized Controlled Trials as Topic; Feeding and Eating Disorders; Bulimia Nervosa; Binge-Eating Disorder; Anorexia Nervosa; Antipsychotic Agents
PubMed: 37393954
DOI: 10.1016/j.jad.2023.06.068 -
Journal of Affective Disorders Sep 2023Transcutaneous auricular vagus nerve stimulation (taVNS) is used for treating depression but the efficacy and safety have not been well assessed. This study was... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Transcutaneous auricular vagus nerve stimulation (taVNS) is used for treating depression but the efficacy and safety have not been well assessed. This study was conducted to evaluate the efficacy and safety of taVNS in depression.
METHODS
The retrieval databases included English databases of PubMed, Web of Science, Embase, the Cochrane Library and PsycINFO, and Chinese databases of CNKI, Wanfang, VIP and Sino Med, and the retrieval period was from their inception to November 10, 2022. The clinical trial registers (ClinicalTrials.gov and Chinese Clinical Trial Registry) were also searched. Standardized mean difference and the risk ratio were used as the effect indicator and the effect size was represented by the 95 % confidence interval. Revised Cochrane risk-of-bias tool for randomized trials and the Grades of Recommendation, Assessment, Development and Evaluation system were used to assess the risk of bias and quality of evidence respectively.
RESULTS
Totally, 12 studies of 838 participants were included. taVNS could significantly improve depression and reduce Hamilton Depression Scale scores. Low to very low evidence showed that taVNS had higher response rates than sham-taVMS and comparable response rates compared to antidepressants (ATD) and that taVNS combined with ATD had comparable efficacy to ATD with fewer side effects.
LIMITATIONS
The number of studies in subgroups was small and the evidence quality was low to very low.
CONCLUSIONS
taVNS is an effective and safe method for alleviating depression scores and had a comparable response rate to ATD.
Topics: Humans; Vagus Nerve Stimulation; Randomized Controlled Trials as Topic; Transcutaneous Electric Nerve Stimulation; Antidepressive Agents; Vagus Nerve; Depressive Disorder
PubMed: 37230264
DOI: 10.1016/j.jad.2023.05.048